Multi-layered SIS tissue graft construct for replacement of cartilaginous elements in situ

ABSTRACT

A reconstructive structure for a cartilaginous element having a plurality of superimposed layers of a small intestine submucosa compressed and secured together and shaped to provide the multilayered reconstructive element of the anatomical shape of the cartilaginous element to be constructed. The method of forming the reconstructive structure includes superimposing the planar layers of the small intestine compressing, securing and cutting to the desired shape. The superimposing is performed so as to maintain the layers substantially planar prior to compressing and securing. The method of reconstructing a cartilaginous element includes removing at least a portion, if not substantially all of the cartilaginous element, but leaving a seed portion, sculpturing the reconstructive structure to the anatomical shape of the cartilaginous element to be reconstructed; positioning the receptive element adjacent to the seed portion and securing it thereto. To reconstruct a joint having two bones separated by a cartilaginous material, the method includes removing any remaining portions of the cartilaginous material down to a bleeding bone site and positioning and securing the reconstructive element to the bleeding bone site. A barrier layer may be provided between the bleeding bone site and the reconstruction element. Also, a defect site without a bleeding bone site may be created and used with a reconstructive element.

This is a division of application Ser. No. 08/628,773 filed Apr. 5, 1996now U.S. Pat. No. 5,788,625.

BACKGROUND AND SUMMARY OF THE INVENTION

The present invention relates generally to cartilaginous reconstructionand more specifically to a method of forming a reconstructive structurefor cartilage elements, reconstructing a cartilage element in situ usingthe reconstructive structure and reconstructing a joint having two bonesseparated by cartilage material.

Researchers in the surgical arts have been working for many years todevelop new techniques and materials for use as grafts to replace orrepair damaged or diseased tissue structures, particularly bones,cartilaginous tissue and connective tissues, such as ligaments andtendons, and to hasten fracture healing. It is very common today, forinstance, for an orthopaedic surgeon to harvest a patellar tendon ofautogenous or homologous origin for use as a replacement for a torncruciate ligament. The surgical methods for such techniques are wellknown. Further, it has become common for surgeons to use implantableprostheses formed from plastic, metal and/or ceramic material forreconstruction or replacement of physiological structures.

It has been reported that compositions comprising the submucosa of theintestine of warm-blooded vertebrates can be used as tissue graftmaterials in sheet form. See U.S. Pat. No. 4,902,508. The preferredsheet compositions described and claimed in that patent arecharacterized by excellent mechanical properties, including highcompliance, a high burst pressure point, and an effective porosity indexwhich allowed such compositions to be used beneficially for vasculargraft constructs.

The graft materials disclosed in that patent are also useful in tendonand ligament replacement applications as described in U.S. Pat. No.5,281,422. When used in such applications the graft constructs appear toserve as a matrix for the growth of the tissues replaced by the graftconstructs. When used in cruciate ligament replacement experiments notonly does the portion of the graft traversing the joint becomevascularized and actually grow to look and function like the originalligament, but the portion of the graft in the femoral and tibial bonetunnels rapidly incorporates into and promotes development of thecortical and cancellous bone in those tunnels. It was believed that suchproperties derived from the sheet structures of the intestinal tissuederived graft constructs. U.S. Pat. No. 5,281,422 also describes inFIGS. 8 and 9 doubling the graft back over itself, one layer on top ofthe other or rolling it concentrically, one layer on top of the other.

An advantage of the intestinal submucosa graft formed for surgicalrepair is its resistance to infection. The intestinal graft material,fully described in the aforesaid patents, have high infectionresistance, long shelf life and storage characteristics. It has beenfound that xenogeneic intestinal submucosa is compatible with hostsfollowing implantation as vascular grafts, ligaments and tendons and isnot recognized by the hosts' immune system as "foreign" and therefore isnot rejected.

As described in U.S. Pat. No. 5,275,826, fluidized intestinal submucosacan be injected into host tissues in need of repair, for example, boneand soft tissue such as muscle and connective tissues. Also described isthe surgical reconstruction of a collagenous meniscus at the interfaceof articulating bones. In such reconstruction a sheet of a first tissuegraft composition, preferably itself comprising intestinal submucosa ofa warm-blooded vertebrate, is formed into a sealed pouch and filled withthe fluidized tissue graft composition of intestinal submucosa.

An object of the present invention is to use the properties ofintestinal submucosa for reconstruction of cartilaginous elements.

Another object of the present invention is to provide a method offorming a reconstructive structure for cartilaginous elements.

An even further object of the invention is to describe the method ofreconstructing cartilaginous element in situ using an intestinalsubmucosa structure.

A still further object of the present invention is to provide a methodfor reconstructing a joint having two bones separated by cartilaginousmaterial. These and other objects are achieved by a reconstructivestructure or construct including a plurality of superimposed layers ofsmall intestine submucosa compressed and secured together and shaped toprovide a solid multi-layer reconstructive element of the anatomicalshape of the cartilaginous element to be reconstructed. Thereconstructed structure is formed by superimposing a plurality of sheetsof small intestinal submucosa. Superimposed layers are compressed andsecured together. The compressed and secured structure is cut andsculptured into the anatomical shape of the cartilaginous element as asolid multi-layered reconstructive structure.

The superimposed layers may be formed by wrapping a continuous piece ofsmall intestinal submucosa about a pair of spaced mandrels. Preferably,the mandrels are positioned to diverge at an acute angle from an apex.This allows the concave edge of the small intestine submucosa to becloser to the apex than the concave edge and therefore compensate forthe varying edge length of the small intestine submucosa. This resultsin a substantially planar structure of the multi-layers. Alternatively,small intestine submucosa is cut into sheets and the sheets aresuperimposed or stacked. The angular orientation of the sheets inparallel plane may be varied.

A clamp or other tool or hydraulic press may be used to compress thesuperimposed layers together and hold them while they are securedtogether. The layer may be secured together by stitching, crimping,quilting, drying or drying in a vacuum.

The clamp may include a slot which serves as a suturing guide. Also, theoutline of the clamp may be used as a cutting guide. In addition tocutting the outline of the desired anatomical shape, the multi-layersmay be sculptured in the cross-section to the desired anatomical shape.

The reconstructive structure just described may be used forreconstructing a cartilaginous element in situ. The method includesremoving at least a portion, if not substantially all of thecartilaginous element, but leaving a seed portion, sculpting areconstructive structure formed of plural layers of small intestinesubmucosa to the anatomical shape of the cartilaginous element beingreconstructed, and positioning it adjacent to the seed portion of thecartilaginous element. The reconstructive element is secured to the seedportion of the cartilaginous element such that the reconstructivestructure forms the substrate for endogenous cartilage growth from theseed portion.

A method for reconstructing a joint having two bones separated by acartilaginous material includes removing any remaining portion of thecartilaginous material down to a bleeding bone site. A reconstructivestructure formed of small intestine submucosa is positioned adjacent tothe bleeding bone site and secured to the bleeding bone site so that thereconstructive structure forms a substrate for cartilaginous growth fromthe bleeding bone site. This provides a cartilaginous layer of materialon the bone site. As an alternative, a membrane or barrier may beinserted to cover the area of the bleeding bone and the reconstructiveelement may be affixed to the membrane or barrier.

If a sufficient amount of cartilaginous material remains on the bone,the cartilage can be abraded to create a uniform defect without takingit to the bleeding bone. A reconstructive element is then attached tothe remaining cartilaginous material.

Other objects, advantages and novel features of the present inventionwill become apparent from the following detailed description of theinvention when considered in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a mandril and method of forming aplurality of layers of small intestinal submucosa according to theprinciples of the present invention.

FIG. 2 is a perspective view of a clamping tool and guide according tothe principles of the present invention.

FIG. 3 is a plan view of a method of clamping and securing according tothe principles of the present invention.

FIG. 4 is a perspective view of cutting the clamped plural layers usingthe clamp as a guide.

FIG. 5 is a perspective view of the cutting step without a guide.

FIG. 6 is a perspective view of the method of preparing the site andattaching the reconstructive structure according to the principles ofthe present invention.

FIG. 7 is a perspective view of a backbone.

FIG. 8 is a cut-away perspective view of a wrist.

FIG. 9 is another cut-away view of a wrist.

FIG. 10 is a cut-away view of a shoulder.

FIG. 11 is a view of a second embodiment forming a plurality of layersfrom sheets of small intestinal submucosa according to the principles ofthe present invention.

FIG. 12 is a diagrammatic view of another method of clamping andsecuring according to the principles of the present invention.

FIG. 13 is a perspective view of the method of securing using quiltingaccording to the principles of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The starting material for the structure in accordance with the presentinvention comprises vertebrate submucosa, most preferably, the tunicasubmucosa along with a basilar portion of the tunica mucosa of a segmentof intestinal tissue of a warm-blooded vertebrate. One preferredstarting material comprises the tunica submucosa along with the laminamuscularis mucosa and the stratum compactum of a segment of smallintestine, said layers being delaminated from both the tunica muscularisand the luminal portion of the tunica mucosa of said segment. Such amaterial is referred to herein as Small Intestine Submucosa ("SIS"). Thethickness and definition of the basilar components of the tunica mucosa,i.e., the lamina muscularis mucosa and the stratum compactum, are knownto be species dependent.

The preparation of SIS from a segment of small intestine is detailed inU.S. Pat. No. 4,902,508, the disclosure of which is expresslyincorporated herein by reference. A segment of intestine, preferablyharvested from porcine, ovine or bovine species, is first subject toabrasion using a longitudinal wiping motion to remove both the outerlayers (particularly the tunica serosa and the tunica muscularis) andthe inner layers (at least the luminal portions of the tunica mucosa).Typically, the SIS is rinsed with saline and optionally stored in ahydrated or dehydrated state until use as described below.

The method of forming a reconstructive structure for cartilaginouselements will be described specifically for a meniscus shapedcartilaginous element as an example. Specifically as discussed withrespect to FIG. 6, it will be the meniscus in the knee joint.

As illustrated in FIG. 1, a length of SIS 10 is wrapped around a mandril20 having legs 22 and 24 connected at bight 26 and diverging therefrom.The SIS 10 includes two lateral edges 12 and 14 of different lengths.This is a natural condition of the material and may be considered aconcave shorter or mesenteric edge 12 and a convex longer oranti-mesenteric edge 14. The diverging angle of the legs 22 and 24 ofthe mandril is selected to compensate for the various lengths of theedges 12 and 14 and to produce flat or planar layers. Without themandril 20, the superimposed layers would have a tendency to buckle orthe SIS would have to be stretched and thereby producing uneven tensionon the surface. Once the number of layers required to duplicate thecartilaginous element to be replaced have been wrapped on the mandrel20, the layers are compressed or clamped together for securing.

Tool 30, illustrated in FIG. 2, includes a pair of arms 32 pivotallyconnected together and terminating in templates or clamping heads 34.The clamping heads 34 have an exterior shape of the cartilaginouselement to be reconstructed. The arms 32 of the clamp 30 may includeinterlocking projections 38 as in other surgical or medical clamps. Aspreviously discussed, this is a meniscus shape. Each head 34 includes aslot 36 which is a guide for suturing the layers together.

As illustrated in FIG. 3, the clamp 30 is applied to the plurality ofthe layers of SIS 10 while on the mandrel 20. One method of securingincludes using a needle 40 and suture 42 to suture through the slot 36in the template 34. Alternative methods of securing the layers togetheris quilting, crimping, drying and drying under a vacuum. All of theseare performed while compressing the layers using the clamp 30 or othershape or style of compression plates or devices or hydraulic pressure.

The secured layers are then shaped by cutting with a knife 46 asillustrated in FIG. 4. Preferably, the clamping heads 34 form a templatefor the cutting as illustrated in FIG. 4. The complete meniscus shapemay be cut using the heads 34 as a template or only one side thereofwith the remainder being cut freehand as illustrated in FIG. 5.Alternatively, the clamp heads 34 may have a peripheral projection andused as a die in a press to cut the layers to the desired shape.

Also, since meniscus and other shapes do not have uniformcross-sections, the sculpturing of the resulting structure 16 may beperformed using the knife 46. Sculpturing is intended to include theoriginal cutting as well as cross-sectional shaping. Thus, a flat planarconstruct illustrated in FIG. 5 may be provided by the surgeon, who thensculptures it to replicate substantially the exact shape of the meniscusrequired for the appropriate patient.

As an alternative method of forming a plurality of superimposed planarlayers of SIS, the SIS 10 may be cut along its length and then cut intoan appropriate size sheets. As illustrated in FIG. 11, the SIS 10 may becut along its concave or shorter edge 12 such that the convex or longeredge 14 is in the center of the strip. This particular selection ofcutting minimizes the variation in size and tension and increases theplanarity. Depending upon the diameter of the SIS, it will have a widthapproximately 1-2 inches. The SIS will then cut into sheets or segments18, for example, 2-3 inches long. Other methods to form the sheets maybe used.

To further remove or compensate for any variance in the individualsheets 18, the sheets may have varying angular orientation as they arestacked, as illustrated in FIG. 11.

As an alternative to the securement of suturing of FIG. 5, the pluralityof superimposed layers of SIS may be compressed between a pair ofcompressor plates 33 in a heating chamber 35 as illustrated in FIG. 12.This dries the compressed structure 16 and secures the plurality oflayers to SIS together. The chamber 35 may be a pressurized chamber andmay either increase the pressure above atmosphere or form a vacuum. Aconstruct 16 has been formed by applying twenty pounds of pressure bythe pressure plates 33 and heating at 40° C. for between 48-72 hours.Additional experiments have been conducted wherein the construct 16 isdried in a vacuum at ambient temperature, from 72 to 96 hours. Thetemperature may vary from ambient to 50° C. The pressure from a vacuumto 40 psi and time may vary to produce desired construct 16. Theparameters are selected to prevent delamination of the plurality oflayers 18 of the construct 16 while producing the desired density of theultimate product. The number of layers may vary between 50, for example,to about 200 layers, depending upon the thickness of the individuallayers, so as to produce an ultimate construct 16 having a thickness,for example, of 4-8 millimeters.

As a further alternative, the plurality of layers of SIS may be securedby quilting as illustrated by the quilting pattern 43 in FIG. 13. Thequilting may be produced either before, during or after drying orpressing. If performed during pressing using pressing plates, anappropriate opening must be provided in the pressing plate 33. Othermethods of securing may be used. It is preferred that the securement beperformed while the plurality of superimposed layers of SIS are beingcompressed.

As an example, the thickness of the meniscus in the knee joint may varybetween four to eight millimeters in an individual, for example. Thus, areplacement reconstructive structure would include between 50 to 200layers or more, depending upon the method of forming the structure 16.The reconstructive structure 16 of FIG. 5 is a solid multi-layerreconstructive structure having the anatomical shape of thecartilaginous element to be reconstructed. By providing the generalshape of the uniform layers of SIS, sculpturing for the individualapplication may be achieved. Securing with suture 44 along the largerexterior radius of the structure 16 permits the securing of the elementsof the unified structure and sculpturing along the other edges dependingupon the structure of the bones to which the cartilaginous element is tobe inserted.

The method of reconstructing a cartilaginous element in situ will bedescribed in FIG. 6 with reference to a meniscus at the knee joint.Although the femur 50 is shown separated from the tibia 52 for sake ofclearer illustration of the invention, the method includes minimuminvasive surgery without the separation of the femur 50 and the tibia52. The lateral and medial condyle of the femur 50 and the lateral andmedial facet of the tibia include particular surfaces 51 and 52respectfully of cartilaginous material. The cartilaginous material 51and 53 are separated by medial meniscus 54 and lateral meniscus 55 whichare secured by ligaments to the femur 50 and tibia 52. A portion ofsecuring ligaments 56 and 57 for the meniscus 54 and 55 are shown.

At least the portion, if not substantially all, of a damagedcartilaginous element or meniscus 54 is removed. Preferably, a seedportion remains. If a small crescent shape is not damaged and remains,it will provide an attachment section for the reconstructive element 16as well as a seed for the growth of the replacement cartilaginouselement. Also, by leaving a crescent shape portion, the ligaments thencan be used to hold the remainder of the meniscus to the bone. Thereplacement cartilaginous element 16 has been attached by suturing,using needle 47 and suture 48 to the remaining portion as illustratedfor the lateral meniscus 55.

If the cartilaginous element or meniscus 54 is not damaged beyondrepair, but only torn, small portions of the damaged cartilaginouselement can be removed and replacement cartilaginous element 16 attachedthereto. Alternatively, a replacement cartilaginous element 16 issculptured to represent the damaged layers and attached directly to thein situ cartilaginous element or meniscus 54. This will strengthen thetorn element without removing it. As discussed above, appropriatesculpturing is performed.

As previously discussed, the surgery is performed by minimal invasionfrom the side of the joint. Well known methods of cutting and suturingmay be performed. If the meniscus 54 and 55 is so damaged such that acontinuous crescent shape is not available for attaching, thereconstructive structure 16 may be attached to the tendon 56, 57 by anyremaining seed section. The seed portion of the meniscus 54, 55 incombination with the synovial fluids support the growth of cartilaginousmaterial using the SIS as a matrix or substrate.

The reconstructive structure of the present invention can also be usedto repair, in situ, the articulation cartilage 51 and 52 on the surfaceof the femur 50 or tibia 52. This produces hyaline cartilage. The areaswhere the method is used is the tibia plateau, the femoral condyle, thefemoral head and acetabula, ankle joint, elbow joint, shoulder joint,finger joints. The desired thickness of the SIS structure 16 is providedand secured to the bone by suturing or tissue adhesive, for example,fibrin glue. The damaged cartilaginous material is scraped down to abloody surface of the bone to allow the necessary seed site for thegrowth of the cartilaginous material. Alternatively, a membrane orbarrier may be inserted to cover the area of the bleeding bone, and thereconstructive element is affixed to that membrane or barrier. A barrieris used to separate the bleeding bone from the reconstructive element,for example, and may include ceramic or a resorbable membrane. Themembrane is secured by tacking or any other method. If the cartilaginousmaterial on the bone is not substantially damaged, the cartilage isabraded to create a uniform damaged area without taking it to thebleeding bone. The reconstructive element is then attached to theremaining cartilaginous material by suturing or using a tissue adhesive.

The same process may be used to replace intervertebral disc. Asillustrated in FIG. 7, the vertebral body 62 is separated byintervertebral disc 64 of cartilaginous material. Reconstruction of anintervertebral disc 64 can be accomplished according to the methoddescribed with respect to FIG. 6 by attaching the SIS shaped disc to aremaining undamaged disc portion. Alternatively, fusion may take placebetween the adjacent vertebral body 62. The broken or splitintervertebral disc 64 is removed down to a bleeding bone. Thereconstructive structure of SIS formed by the method described to FIGS.1-5 or 11-13 is inserted between the vertebral body 62. The bloody bonebecomes the seed site and the SIS reconstructive structure forms amatrix for forming a bony structure. This is an example of afibrocartilage structure. Other formations of the fibro structure wouldbe the symphysis pubis mandibular joint and sterno clavicular joint.

Other types of cartilage or elastic cartilage is used in reconstructivesurgery to model facial features such as nose and ears. Thereconstructive structure formed according to the method of FIGS. 1-5 maybe used for the substrate or reconstruction of elastic cartilage.

As illustrated in FIG. 8, a cartilaginous meniscus 70 and particulardisc 72 in the wrist may be restructured using the present method.Similarly, as illustrated in FIG. 9, the radiocarpal articulation 74 andthe intercarpal articulation 76 in the hand. may also be reconstructedusing the method of the present invention.

As illustrated in FIG. 10, the particular cartilage 80 on the humerus 82rides on the cartilage 84 in the glenoid cavity of the scapula 86. Boththe particular cartilage 82 and the cartilage of the glenoid cavity 84may be replaced using the method of the present invention.

Although the present invention has been described and illustrated indetail, it is to be clearly understood that the same is by way ofillustration and example only, and is not to be taken by way oflimitation. The spirit and scope of the present invention are to belimited only by the terms of the appended claims.

What is claimed:
 1. A tissue graft construct for the replacement orrepair of a cartilaginous structure that is located between, and indirect contact with, two bones, said tissue graft construct comprising:aplurality of layers of intestinal submucosa secured together to form asolid multilayered construct having about 50 to about 200 layers and athickness of about 4 to about 8 mm, wherein the multilayered constructis sculptured to have the anatomical shape of the cartilaginousstructure to be replaced or repaired.
 2. The tissue graft construct ofclaim 1, wherein said layers of intestinal submucosa are fused together.3. The tissue graft construct of claim 2, wherein the construct has theshape of a meniscus.
 4. The method of claim 1, wherein said layers ofintestinal submucosal are secured by sutures.